D-Gulose was first prepared by Emil Fischer in 1891. [Fischer, et al, Ber., 24, 532 (1891)] During the past 100 years, several other syntheses of D-gulose have been reported, including the following: van Ekenstein, Blanksma, Rec. Trav. Chim., 27, 3 (1908); Meyer zu Reckendorf, Angew. Chem. Int. Ed., 6, 177 (1967); Koster, et al. Angew. Chem. 92, 553 (1980).
D-Gulose is an aldohexose sugar which does not occur in nature. Since no natural source of the sugar exists, its preparation by artificial means is required. One obstacle to the commercial development of D-gulose has been that a crystalline, free flowing, highly pure highly pure form of D-gulose has not been previously known. The Merck Index, Tenth Edition, 4459-4460 (1983) discloses that D-gulose is a syrup.
Many monosaccharides are known to exist in multiple crystalline forms which vary with respect to physical and chemical properties. For example, the common sugar D-glucose exists in two different isomeric forms, .alpha.-D-glucopyranose and .beta.-D-glucopyranose. ##STR1##
Both D-glucose isomers have been isolated in pure form. Although they do not differ in elementary composition, their physical and chemical properties differ as shown in the following table:
TABLE ______________________________________ PROPERTIES OF .alpha.- AND .beta.-D-GLUCOPYRANOSE PROPERTY .alpha.-D-glucopyranose .beta.-D-glucopyranose ______________________________________ Specific rotation +112.2.degree. +18.7.degree. Melting point, .degree.C. 146 150 Solubility in H.sub.2 O, 82.5 178 g per 100 mL Relative rate of oxida- 100 &lt;1.0 tion by glucose oxidase ______________________________________
Taste and sweetness level is also a function of the crystalline form of a sugar. For example, crystalline .alpha.-D-mannopyranose is about half as sweet as glucose. On the other hand, crystalline .beta.-D-mannopyranose is distinctly bitter. Also, crystalline .beta.-D-fructopyranose tastes almost twice as sweet as sucrose while an aqueous solution of D-fructose, which exists as a mixture of several isomeric forms, is approximately equal to the sweetness of sucrose.
The novel crystalline D-gulose of this invention has been determined to consist entirely of the pure isomer .beta.-D-gulopyranose. In this crystalline form, .beta.-D-gulopyranose has been found to possess many desirable features which were not available from syrupy D-gulose. For example, it is free flowing, non-hygroscopic, highly pure and has a clean sweet taste. In this form, .beta.-D-gulopyranose is useful, for example, as an excipient, a chelating agent, a pharmaceutical intermediate, a cleaning agent for glass and metals, a food additive, and as an additive for detergents.
In such applications, it is a very desirable feature to have a crystalline, free flowing form of D-gulose. For example, as an excipient, crystalline .beta.-D-gulopyranose may be combined with an active drug for preparing a convenient, agreeable dosage form, such as a tablet. As a food additive, crystalline D-gulose can be used in applications such as dry, prepared mixes for making beverages, cakes puddings and the like. As a pharmaceutical intermediate, crystalline .beta.-D-gulopyranose may be used in chemical processes where water is detrimental or where high purity is required to avoid formation of toxic by-products.
In the preparation of D-gulose by Koster, et at, Angew. Chem., 92(7) 553 (1980), the final product obtained was a water free glassy solid which could be ground to a very hygroscopic white powder. The powder softened over a broad temperature range (60.degree.-80.degree. C.) to give a clear melt at 80.degree. C. Another solid was obtained by precipitating the D-gulose from ethanol with diethyl ether, but no melting range or other physical properties are given for this second product.
Van Hook and Mac Innes, Sugar Journal, 16(5), 20(1953) describes the crystallization by sonic irradiation of several sugars including arabinose, fructose, sorbitol, gulose, and others. In this article no physical properties are given and it is not specified whether D-gulose or L-gulose was crystallized.